The effect of hypokalemia on the mechanism of renal concentrating ability has been studied in dogs on a 115 mEq sodium, 55 mEq potassium/day intake by the administration of desoxycorticosterone acetate (DOCA) 25 mg/day, i.m., for 6 days. Potassium depletion was paralleled by polyuria and elevated urinary PGE2 excretion in the presence of significanly elevated serum sodium concentration, and persisted during the 4-day post-DOCA control period. PRA was suppressed throughout the entire experimental protocol. We conclude that hypokalemia may stimulate renal PGE2 biosynthesis, presumably in the collecting duct epithelial cells and thereby may impair renal concentrating ability. Similar studies are being conducted in human subjects.